Effect of radioprotectors on the aggregability, cAMP and thiol content of blood platelets

Aminothiol radioprotectors (MEA, AET, WR-1065) were found to be inhibitors of platelet aggregation. The aim of this study has been to clarify the potential involvement of the adenylate cyclase-cAMP system in this effect. In vitro aminothiol compounds (> 1 mmol/l) inhibited platelet function as well as AC-activity, i.e. significantly reduced their cAMP content. In less than 1 mmol/l concentration WR-1065 elevated the cAMP content of PGI2-stimulated platelets, while basal cAMP level mainly remained unchanged. On the effect of WR-1065 the level of non-protein thiols (NP-SH) markedly elevated in the platelets, while their protein-bound thiol content (PB-SH) either decreased or remained at control level. The phosphorothioate WR-2721 was effective only after in vitro or in vivo dephosphorylation. Although the amount of NP-SH slightly increased, the PB-SH content decreased in the platelets isolated after intravenous administration of WR-2721. Moreover, platelet-poor plasma samples of WR-2721 treated animals also inhibited both the AC-activity and function of control platelets, too. Based on these results it is suggested that aminothiol radioprotectors non-specifically inhibit platelet functions forming mixed disulfides with endogenous, mostly protein-bound thiols. The slight elevation of AC-activity caused by low doses of WR-1065 also suggest that the AC-complex consists of unevenly sensitive subunits (G-proteins, catalytic subunit).